rs2989722

Positions:

• chr9-134914641-G-A
• chr9-134914641-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002003.5(FCN1):​c.271+115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 923,456 control chromosomes in the GnomAD database, including 162,056 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (21997 hom., cov: 30)
  • Exomes 𝑓: 0.60 (140059 hom.)
• Consequence: FCN1 NM_002003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

FCN1 (HGNC:3623): (ficolin 1) The ficolin family of proteins are characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. The collagen-like and the fibrinogen-like domains are also found separately in other proteins such as complement protein C1q, C-type lectins known as collectins, and tenascins. However, all these proteins recognize different targets, and are functionally distinct. Ficolin 1 encoded by FCN1 is predominantly expressed in the peripheral blood leukocytes, and has been postulated to function as a plasma protein with elastin-binding activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN1	NM_002003.5	c.271+115C>T		intron_variant		ENST00000371806.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN1	ENST00000371806.4	c.271+115C>T		intron_variant		1	NM_002003.5	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79321 AN: 151704 Hom.: 22005 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.598 AC: 461595 AN: 771636 Hom.: 140059 AF XY: 0.601 AC XY: 238609 AN XY: 396742

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.610

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.641

Gnomad4 NFE exome AF: 0.629

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.523 AC: 79327 AN: 151820 Hom.: 21997 Cov.: 30 AF XY: 0.526 AC XY: 39039 AN XY: 74172

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.507

Alfa AF: 0.450 Hom.: 1382

Bravo AF: 0.494

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2989722; hg19: chr9-137806487;